1. Field of the Invention
This invention generally relates to integrated circuit (IC) fabrication and, more particularly, to a fine resolution sensor with an iridium oxide nanowire neural interface.
2. Description of the Related Art
FIGS. 1A through 1C depict the placement of optical electrodes, using epiretinal and subretinal approaches (prior art). Studies show that blind patients with retinitis pigmentosa and masular degeneration can observe a visual percept induced by the direct electrical stimulation of the retina. Recently, retinal prosthesis development has progressed along two directions. The epiretinal approach places electrode in the vitreous fluid, attached to the surface of the retina, while the subretinal approach places electrodes on the outside of retina, wedged between the photoreceptors and the pigment epithelium. FIG. 1C shows the electrode positions for both type of retina prosthesis.
One major difficulty with the epiretinal approach is that the tissue has a very high resistance to electrical stimulation. This high electrical resistance is due to the fact that the retinal is covered by the inner limiting membrane, similar to the blood-brain barrier, and it is impermeable to many types of ions. Since electrical stimulation depends on electrical current building an electrical field across the target nerve cell, a high-resistance barrier in the stimulation pathway prevents current passage. Thus, current is diverted away to other, lower-resistance tissues. To compensate for this loss, the epiretinal approach requires a much larger charge at the electrode surface, to achieve the same stimulation level on the target tissue as a conventionally functioning eye. In human trials, a net charge of ˜1 uC (micro-Coulomb) is required for the epiretinal approach, a very high charge for neural stimulation, when compared to 50 nC, which is the level typically required for central nervous system stimulation and subretinal stimulation.
One way to overcome the high-impedance barrier of the epiretinal approach is to penetrate the inner limiting membrane. Arrays of sharp electrodes have been fabricated from silicon and have been used for this purpose. Recently, new techniques promise nano-scale piecing wire electrodes, which can be formed by electrodeposition on a glass substrate contoured to fit the retina.
The subretinal prosthesis avoids the high-impedance barrier problem, by installing electrodes behind the retina. The electrodes are also very close to the bipolar cells, allowing easy (low-charge) stimulation. Low thresholds in the range of 2.8 to 100 nC/cm2 have been reported. However, 178 uC/cm2 is a more realistic number. Subretinal prostheses requires that all components be fitted behind the retina, with the circuits integrated with the electrodes. Power is transferred into the eye via light, which in theory is received by integrated photovoltaic cells, to activate the circuitry. The power output needs to be strictly controlled, since heat dissipation is limited in the subretinal space, and overheating can easily damage the retina.
One technical challenge is the trade-off between electrode density and stimulation charge. Although the total charge injection required to elicit a visual percept is fixed, the maximum charge an electrode can deliver is limited by its surface area. Surpassing this charge density threshold generates undesirable and irreversible electrochemical reactions. In order to elicit a visual percept, the charge density requirement dictates that the electrode must have a total surface area of 1 mm2. When considering the limited area of the retinal implant, this constraint translates into a resolution of 5×5 (25 pixels). However, a visual resolution of at least 25×25 pixels (625 pixels) is desired for recovery of functional sight.
To inject more charge without hydrolysis, an electrode made from a material with a higher injection limit can be used, such as iridium oxide (IrOx). As a biocompatible electrode material, IrOx has advantages over Au and Pt and Pt. Au quickly dissolves when a high potential is applied. Pt has the longest history as an electrode material and is the best characterized. Compared to IrOx, the performance of Pt is limited because it cannot sustain as much reversible faradic charge, and it catalyzes water electrolysis at low voltages, limiting its charge-injection capability. Compared to Pt, an IrOx electrode can inject much more charge for a given voltage swing, by cycling iridium through many oxidation states. Because iridium can exist in many valence states with an insignificant change in atomic size, an iridium electrode can cycle from metallic form (Ir) to higher oxidized form (IrO4) reversibly, allowing it to have a high charge-injection limit of 1 mC/cm2. Using cyclic voltammetry with scan rates of 0.06V/s or slower, a charge injection of >25 mC/cm2 can often be obtained. This behavior is attributed to IrOx porous structure, which requires ionic species to diffuse into deep recessed regions to access the full surface area, as well as due to its many oxidation states, requiring the completion of one state change before proceeding to the next reaction. IrOx is especially ideal for applications with slower stimulation waveforms. For neural stimulation, a current pulse longer than 200 us can be employed. Furthermore, IrOx needs to be biased so that its oxidation state is between Ir3+ and Ir4+ to prevent dissolution that occurs at metallic or higher oxidation states. However, because it relies heavily on faradic reactions, IrOx is slower in delivering current.
A second approach to increasing electrode charge-injection involves enlarging the electrode surface area. The surface area of an electrode is a strong function of its geometry. The area of a solid post electrode can be increased by a factor of 10 easily if it is formed into an array of nanowires/tubes/rods.
FIG. 2 is a schematic diagram modeling the interface between an electrode and chemically active solution (prior art). Electrodes pass charge mainly through two mechanisms: faradic reactions and capacitive charging. Capacitive charging is the accumulation of charge at the interface between electrons in a metal electrode and ions adjacent to the electrode in a solution, and is represented by CE. A faradic reaction is the transfer of electrons with ions in a solution by a redox reaction of metal species, and is represented by RE. Both the capacitive and faradic components increase linearly with the electrode area because more charge can accumulate at the interface area and be transferred through chemical reactions by increasing the size of the electrode. This larger electrode can be modeled as having a smaller RE and bigger CE, leading to an increased electrode current at a given potential. Pulses of either constant voltage or current can be used for electrical stimulation. Most frequently, pulses of constant current are used.
FIG. 3 is a partial cross-sectional view comparing a conventional flat electrode with an electrode array (prior art). Micro-machined neural-stimulating electrode array technology has also been researched. The micro-machined electrode has the advantage of providing additional surface area to decrease the current density, while increasing the electrode density and avoiding material corrosion. However, a key issue to be resolved is the fabrication of an electrode array that can conform to the concave shape of the foveal pit. For example, such as array would need to be formed on a flexible substrate (e.g., polyimide).
Another limitation associated with micromachining technology is size, as the individually machined electrodes cannot be made to a nano-size resolution. Even if a template of nano-sized structures could be micro-machined, plating an array of nanostructures, with a noble metal for example, in a sufficiently high aspect ratio is a big challenge. Micro-machined electrodes are normally formed from a thick film that is deposited using a physical vapor deposition (PVD) process or electrode plating. In either case, the resultant film, and micro-machined electrode post are typically a polycrystalline material.
Thus, research is ongoing in the investigation of nanowire-based neuron electrode arrays that can be used to promote the growth of subcellular highways via controlled electrical stimulation. Combined with quantum dots assisted imaging technology, these subcellular highways have potential in image transportation. Nanowire neuron arrays also have the potential to guide movement of drugs and other factors on subcellular highways. These applications may become important in therapy for conditions involving the defective transport of neurons and neurodegenerative disease, for example: Alzheimer's, Huntington's, Parkinson's, and acute brain injury.
Some challenges facing conventional neuron stimulating and recording electrodes are the lack of resolution in micro-fabricated structures. Poor resolution makes in impossible to stimulate subcellular regions of a single cell. This issue can be addressed with the use of grown nanostructures. Experiments with conductive carbon nanotubes (CNTs) have been conducted to test their effectiveness in neural guidance. However, CNTs are prone to bending and warping, and lack the robustness required for repeatable sensitive electrical measurements.
On the other hand, IrOx nanowire-based neuron electrode have a better surface to volume ratio, as compared to CNTs, as well as a high resolution stimulation, biocompatibility, and ability to grow on transparent conducting electrodes such as ITO, SnO2, ZnO and TiO2 with or without any doping.
Single-crystal IrO2 nanowires/rods/tips have a much longer life than polycrystalline IrO2, due to their higher chemical reaction resistance. Single-crystal IrOx nanostructures also have a higher conductance than polycrystalline IrO2, so they can pass through current more efficiently. However, it is difficult to form single-crystal IrO2 films using conventional PVD or electrode plating methods. IrO2 nanostructures can be formed using a solution method, but these structures have a low mechanical strength and poor crystal quality. Vapor phase transport methods can also be used to form IrO2 nanostructures, but this process requires high substrate temperature, and it is not suitable for use with glass and polyimide substrates.
A technology that can grow free standing highly crystallized nanowires/tubes/rods array of IrOx on highly resolved areas of electrode would be useful in the fabrication of a neuron interface.